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1.
A Novel ZRS Mutation Leads to Preaxial Polydactyly Type 2 in a Heterozygous Form and Werner Mesomelic Syndrome in a Homozygous Form 下载免费PDF全文
Yuan Xue Donna Daentl Ethylin Wang Jabs William R. Wilcox Nadav Ahituv 《Human mutation》2014,35(8):945-948
Point mutations in the zone of polarizing activity regulatory sequence (ZRS) are known to cause human limb malformations. Although most mutations cause preaxial polydactyly (PPD), triphalangeal thumb (TPT) or both, a mutation in position 404 of the ZRS causes more severe Werner mesomelic syndrome (WMS) for which malformations include the distal arm or leg bones in addition to the hands and/or feet. Of more than 15 reported families with ZRS mutations, only one homozygous individual has been reported, with no change in phenotype compared with heterozygotes. Here, we describe a novel point mutation in the ZRS, 402C>T (AC007097.4:g.105548C>T), that is transmitted through two Mexican families with one homozygous individual. The homozygous phenotype for this mutation, WMS, is more severe than the numerous heterozygous individuals genotyped from both families who have TPT and PPD. A mouse transgenic enhancer assay shows that this mutation causes an expansion of the enhancer's expression domain in the developing mouse limb, confirming its pathogenicity. Combined, our results identify a novel ZRS mutation in the Mexican population, 402C>T, and suggest that a dosage effect exists for this ZRS mutation. 相似文献
2.
Hongwei Zhu Guodong Wang Donglei Xie Bo Cai Yumin Liu Xingzhong Zhao 《Biomedical microdevices》2014,16(3):479-485
This work reports a facile microfluidic device for Au-nanoparticle enhanced fluorescence detection of tiny amount of nucleotides within droplets in a high-throughput way. Droplets containing single strand DNA probe and relevant complementary strands DNA(cDNA) are generated in flow-focusing manner and the hybridization between them is realized in droplets flowing along a long serpentine channel. In order to find the optimal experimental condition, finite element method simulation is used to predict the interface evolution between the two phase liquids. Based on the fluorescence emited by intercalator reacted with the generated double-strand DNA(dsDNA), the target cDNA with a concentration of 1nM can be detected in droplets. And when we adopt Au nanoparticles to immobilize DNA probe which can amplify the fluorescence intensity, 10pM completary DNA could be detected. Due to the advantages in high-throughput and compartmentalization of this droplet platform, the detection procedure can be finished in 3 h. Our method shows good potential application in facile, sensitive, low cost and fast DNA detection for applications in personal health care. 相似文献
3.
Vaishnavi Srinivasaraghavan Jeannine Strobl Dong Wang James R. Heflin Masoud Agah 《Biomedical microdevices》2014,16(5):689-696
The relative sensitivity of standard gold microelectrodes for electric cell-substrate impedance sensing was compared with that of gold microelectrodes coated with gold nanoparticles, carbon nanotubes, or electroplated gold to introduce nano-scale roughness on the surface of the electrodes. For biological solutions, the electroplated gold coated electrodes had significantly higher sensitivity to changes in conductivity than electrodes with other coatings. In contrast, the carbon nanotube coated electrodes displayed the highest sensitivity to MDA-MB-231 metastatic breast cancer cells. There was also a significant shift in the peak frequency of the cancer cell bioimpedance signal based on the type of electrode coating. The results indicate that nano-scale coatings which introduce varying degrees of surface roughness can be used to modulate the frequency dependent sensitivity of the electrodes and optimize electrode sensitivity for different bioimpedance sensing applications. 相似文献
4.
Haiying Luo Chongzhen Wang Meifu Feng Yong Zhao 《International journal of medical sciences》2014,11(1):87-96
Background: Decline immune function is well documented after spaceflights. Microgravity is one of the key factors directly suppressing the function of immune system. Though T cell immune response was inhibited by microgravity, it is not clearly whether activation would be inhibited after a pre-exposure of microgravity on T lymphocytes at the resting state. Methods: We herein investigated the response ability of resting CD4+ and CD8+ T cells experiencing pre-exposure of modeled microgravity (MMg) for 0, 8, 16 and 24 hrs to concanavalin A (ConA) stimulation. The phenotypes and subsets of immune cells were determined by flow cytometry. Results: Both CD4+ and CD8+ T cells with an MMg pre-exposure exhibited decreased expressions of activation-markers including CD25, CD69 and CD71, inflammatory cytokine secretion and cell proliferation in response to ConA compared with T cells with 1g controls in an MMg exposure time- dependent manner. Moreover, short term MMg treatment caused more severe decreased proliferation in CD4+ T cells than in CD8+ T cells. Conclusions: MMg can directly impact on resting T cell subsets. CD4+ T cells were more sensitive to the microgravity inhibition than CD8+ T cells in respect of cell proliferation. These results offered new insights for the MMg-caused T cell functional defects. 相似文献
5.
6.
Li-Li Wang Hui Gu Yang Fan Yi Zhang Di Wu Jia-Ning Miao Tian-Chu Huang Hui Li Zheng-Wei Yuan 《International journal of medical sciences》2014,11(3):262-267
Background: In a subset of patients with Hirschsprung''s disease (HSCR), gastrointestinal motor dysfunction persisted long after surgical correction. Gastrointestinal motility is achieved through the coordinated activity of the enteric nervous system, interstitial cells of Cajal, and smooth muscle (SMC) cells. Inhibition of four-and-a-half LIM protein-1 (Fhl1) expression by siRNA significantly decreases pulmonary artery SMCs migration and proliferation. Furthermore when up-expressing FHL1 in atrial myocytes, K (+) current density markedly increases, therefore changing myocytes'' response to an electrical stimulus. However whether FHL1 in colon SMCs (the final effector organ) influences intestinal motility in HSCR patients has not been clarified. Methods: FHL1 mRNA and protein expressions were analyzed in 32 HSCR colons and 4 normal colons. Results: Smooth muscle layers were thicken and disorganized in HSCR. FHL1 was expressed in the ganglion cells of the myenteric plexus, submucosa, as well as in the longitudinal and circular muscle layer of the ganglionic colon. FHL1 mRNA relative expression level in aganglionic colons was 1.06±0.49 (ganglionic colon relative expression level was 1) (P=0.44). FHL1 protein gray level relative to GAPDH in normal colons was 0.83±0.09. FHL1 expression level in ganglionic colon (1.66±0.30) or aganglionic colon (1.81±0.35) was significantly higher than that in normal colons (P=0.045 and P=0.041, respectively). Meanwhile, we found FHL1 expression in aganglionic colon was slightly stronger than that in ganglionic colon (P=0.036). Conclusion: These data suggested that up-regulated FHL1 in smooth muscle in HSCR might be associated with intestinal wall remodeling in HSCR and might be one of the risk factors for gastrointestinal motor dysfunction. 相似文献
7.
Sung-Nan Pei Ming-Chun Ma Huey-Ling You Hung-Chun Fu Ching-Yuan Kuo Kun-Ming Rau Ming-Chung Wang Chien-Te Lee 《International journal of medical sciences》2014,11(6):614-619
Background: Genome-wide-association studies have identified the TMPRSS6 polymorphism rs855791 has the strongest association with red blood cell indices or iron parameters in general population. Whether this genetic variant influences the susceptibility of iron deficiency anemia (IDA) in women with menstruation has not been well studied.Methods: In this case-control study, we enrolled 67 women with IDA and 107 healthy volunteers, and analyzed their complete blood counts, rs855791 genotypes, and menstrual amounts. Menstrual blood loss was evaluated with a pictorial blood-loss assessment chart.Results: There were significantly fewer rs855791 C homozygotes in the IDA group than in the healthy group (11.9% vs. 25.2%, p = 0.03). The odds ratio (OR) of C homozygotes having IDA versus non-CC subjects having IDA was 0.4 (95% CI, 0.17 - 0.95, p = 0.04). When the analysis was confined to study subjects with menorrhagia, this difference became more prominent (9.6% vs. 28.6%, p = 0.01; OR, 0.27, 95% CI, 0.09 - 0.77, p = 0.01). For women with non-CC genotypes, there was an inverse correlation between hemoglobin levels and menstrual loss (p < 0.001); however, this association was not found for those with genotypes CC (p = 0.15).Conclusions: Our study suggests homozygosity for TMPRSS6 rs855791 C genotype has a protective role against IDA in women at reproductive age, especially in those with menorrhagia. 相似文献
8.
YanGang Wang Luan Wang EnZe Li Yang Li ZhongChao Wang XiaoFang Sun XiaoLong Yu Lin Ma YunLong Wang YouXin Wang 《International journal of medical sciences》2014,11(9):880-885
Background The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects.Methods In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells (WHC) and C-reactive protein (CRP). This trial is registered at ISRCTN.org as trial ISRCTN65219941.Results A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group (CH group) and the Colchicine group (Col group) were 12.50% vs 14.77% (difference -2.22%, 95% confidence interval (95% CI): -10.78%~6.23%), meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events (mainly diarrhea) was less in the Col group than in the CH group (2.27% vs 28.41%, 95% CI 0.01~0.26). In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group (P<0.05).Conclusions The Chuanhu anti-gout mixture was non-inferior to colchicine for the treatment of acute gouty arthritis. The study suggested that the Chuanhu anti-gout mixture can be considered an alternative choice for the treatment of acute gouty arthritis because of its lower incidence of adverse events and its protection of kidney and renal function. 相似文献
9.
Kai Liu Bai Ji Wei Zhang Songyang Liu Yingchao Wang Yahui Liu 《International journal of medical sciences》2014,11(9):893-896
Objective: This retrospective study compared the advantages and disadvantages of iodine-125 (125I) seed implantation and pancreaticoduodenectomy (PD) in the treatment of pancreatic cancer.Methods: Patients with diagnosed pancreatic cancer who were treated with 125125I seed implantation (30 patients) or PD (30 patients) in our hospital were evaluated for operative time, bleeding, liver function, time to first bowel movement and normal diet, survival, and medical costs.Results: Compared with patients who underwent PD, those given 125I seed implantation had significantly shorter operative time, less bleeding, higher albumin, shorter periods to bowel movement and normal diet, lower risk of complications, and lower medical costs (P < 0.001, each). The difference of bilirubin level, time to feeding, and median survival were not significant statistically between two treatment grouops.Conclusion: For pancreatic cancer patients for whom PD is not appropriate or who refuse PD, 125I seed implantation is a good option. 相似文献
10.
Weiming Qiu Mingxing Lei Jin Li Ning Wang Xiaohua Lian 《International journal of medical sciences》2014,11(10):1022-1028
Sebaceous glands (SGs) undergo cyclic renewal independent of hair follicle stem cells (HFSCs) activation while HFSCs have the potential to differentiate into sebaceous gland cells, hair follicle and epidermal keratinocytes. Abnormalities of sebaceous gland progenitor cells contribute to the development of sebaceous neoplasms, but little is known about the role of HFSCs during sebaceous neoplasm development. Here, using dimethylbenzanthracene (DMBA) plus 12-o-tetradecanoyl phorbol-13-acetate (TPA) treatment developing sebaceous neoplasms (SNs) were identified with H&E and Oil red O staining. And then the molecular expression and activation of HFSCs and was characterized by immunostaining. Wnt10b/β-catenin signaling molecular which is important for activation of HFSCs were detected by immunostaining. We found hair follicle and epidermal cell markers were expressed in sebaceous neoplasms. Furthermore, SOX-9 and CD34-positive HFSCs were located in the basal layer of sebaceous lobules within the sebaceous neoplasms. Many appear to be in an active state. Finally, Wnt10b/β-catenin signaling was activated within the basal cells of sebaceous lobules in the sebaceous neoplasms. Collectively, our findings suggest that the abnormal activation of both HFSCs and Wnt10b/β-catenin signaling involves in the development of sebaceous neoplasms. 相似文献